Vitamin D Binding Protein, a Ligand of Integrin beta 1, Motivates Both Tumor Cells and Schwann Cells to Promote Perineural Invasion in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Perineural invasion (PNI) is a common pathological characteristic of pancreatic ductal adenocarcinoma (PDAC), closely linked to postoperative recurrence, metastasis, and unfavorable prognosis. Nevertheless, the precise mechanisms that govern PNI in PDAC remain poorly elucidated. Here, group-specific component protein (GC) is identified as one of the most significantly upregulated genes related to PNI, primarily derived from malignant ductal cells compared to other cell types. GC knockdown attenuates PDAC cell invasiveness toward nerves, and this effect operates independently of vitamin D transport. Moreover, GC protein activates Schwann cells by inducing a dedifferentiation program, and enhances the mutual chemoattraction between PDAC cells and Schwann cells. Mechanistically, integrin β1 (

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12667536 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature